TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27360	82303;82304;82305	chr2:178564054;178564053;178564052	chr2:179428781;179428780;179428779
N2AB	25719	77380;77381;77382	chr2:178564054;178564053;178564052	chr2:179428781;179428780;179428779
N2A	24792	74599;74600;74601	chr2:178564054;178564053;178564052	chr2:179428781;179428780;179428779
N2B	18295	55108;55109;55110	chr2:178564054;178564053;178564052	chr2:179428781;179428780;179428779
Novex-1	18420	55483;55484;55485	chr2:178564054;178564053;178564052	chr2:179428781;179428780;179428779
Novex-2	18487	55684;55685;55686	chr2:178564054;178564053;178564052	chr2:179428781;179428780;179428779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-140
• Domain position: 83
• Structural Position: 169
• Q(SASA): 0.1694
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/L	rs764393169	-0.292	0.164	N	0.339	0.095	0.533131753447	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/T	None	None	0.684	N	0.593	0.34	0.651931416193	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02462E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.5674	likely_pathogenic	0.6265	pathogenic	-1.269	Destabilizing	0.373	N	0.529	neutral	None	None	None	None	N
I/C	0.6726	likely_pathogenic	0.709	pathogenic	-1.032	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	N
I/D	0.894	likely_pathogenic	0.9234	pathogenic	-0.682	Destabilizing	0.91	D	0.716	prob.delet.	None	None	None	None	N
I/E	0.7931	likely_pathogenic	0.8423	pathogenic	-0.653	Destabilizing	0.59	D	0.705	prob.neutral	None	None	None	None	N
I/F	0.124	likely_benign	0.1444	benign	-0.704	Destabilizing	0.953	D	0.617	neutral	None	None	None	None	N
I/G	0.8602	likely_pathogenic	0.889	pathogenic	-1.581	Destabilizing	0.742	D	0.708	prob.delet.	None	None	None	None	N
I/H	0.611	likely_pathogenic	0.677	pathogenic	-0.6	Destabilizing	0.987	D	0.69	prob.neutral	None	None	None	None	N
I/K	0.6511	likely_pathogenic	0.7184	pathogenic	-0.971	Destabilizing	0.007	N	0.519	neutral	N	0.446475136	None	None	N
I/L	0.1015	likely_benign	0.107	benign	-0.487	Destabilizing	0.164	N	0.339	neutral	N	0.451057023	None	None	N
I/M	0.1215	likely_benign	0.1352	benign	-0.619	Destabilizing	0.939	D	0.634	neutral	N	0.481206572	None	None	N
I/N	0.5021	ambiguous	0.571	pathogenic	-0.974	Destabilizing	0.91	D	0.718	prob.delet.	None	None	None	None	N
I/P	0.9621	likely_pathogenic	0.9657	pathogenic	-0.717	Destabilizing	0.953	D	0.722	prob.delet.	None	None	None	None	N
I/Q	0.6423	likely_pathogenic	0.7036	pathogenic	-1.051	Destabilizing	0.91	D	0.718	prob.delet.	None	None	None	None	N
I/R	0.5462	ambiguous	0.6294	pathogenic	-0.44	Destabilizing	0.792	D	0.715	prob.delet.	N	0.474760602	None	None	N
I/S	0.505	ambiguous	0.5769	pathogenic	-1.565	Destabilizing	0.742	D	0.657	neutral	None	None	None	None	N
I/T	0.4543	ambiguous	0.5195	ambiguous	-1.407	Destabilizing	0.684	D	0.593	neutral	N	0.44391762	None	None	N
I/V	0.0812	likely_benign	0.0894	benign	-0.717	Destabilizing	0.004	N	0.161	neutral	N	0.378175418	None	None	N
I/W	0.775	likely_pathogenic	0.8146	pathogenic	-0.774	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
I/Y	0.4913	ambiguous	0.5342	ambiguous	-0.551	Destabilizing	0.984	D	0.658	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.